A randomised double-blind placebo-controlled trial of the effect of inhaled heparin on lung function, hyperinflation and exercise capacity in patients with COPD

Unfractionated heparin (UFH) is a drug with a structurally diverse molecular scaffold naturally oriented to multiple targets. Previous studies have indicated inhalation of UFH treats local inflammation, mucus hypersecretion and lung injury, without systemic anticoagulation, and is safe.

In this study, forty patients with moderate to severe COPD admitted to the IRCCS San Raffaele Pisana for 21 days rehabilitation were randomised to receive inhaled UFH (75,000 or 150,000 IU BID) or placebo for 21 days. All patients also received nebulised salbutamol (1 mg) and beclomethasone (400 µg) BID over the same period. Lung function was measured at day 0, 7, 14 and 21 of treatment, and at a follow-up visit 7 days post-treatment. Hyperinflation (IC, RV, TLC), exercise capacity (6MWT) and dyspnoea (Borg score) were measured before and after treatment.

At both doses, UFH significantly increased FVC following 7 days of treatment and 150,000 IU BID significantly increased FEV1 (+249±69 ml compared with placebo) at this time point, an effect maintained to the 28 day follow-up.

At the high dose, UFH significantly increased IC (+550±142 ml), reduced TLC (-2.27±0.64 L) and RV (-1.00±0.43 L) compared with placebo at day 21. This effect on air trapping resulted in clinically significant improvement in exercise capacity and dyspnoea. There were no serious adverse events or effects on systemic coagulation.

These clinically significant effects of inhaled UFH relate to the ability of heparin to inhibit multiple targets which may provide an effective way of treating complex diseases such as COPD to improve on current therapeutic strategies.